Blood, sweat and cells: The making of New Zealand’s first CAR T-cell trial

Brigitta’s office for many years was nestled at the end of the first-floor corridor opposite the most tightly controlled labs at the institute. These labs contain machines that look like they’ve come straight out of a sci-fi novel.

These sleek, pearly capsules, aptly named Cocoons, gently rock newly formed CAR T-cells from side to side, nurturing them and creating the optimal conditions for them to grow. 

Safeguarded by layers of automation and quality control, each Cocoon is designed to reprogramme a patient’s own immune cells into a cancer therapy, personalised just for them. For these patients, many of whom have exhausted every other treatment for their blood cancer, the cells are a last chance.

The Malaghan’s ENABLE CAR T-cell clinical trial programme, now in phase 2, represents the culmination of monumental effort by many. Brigitta has been pivotal at every step of the Malaghan Institute’s journey to bring this revolutionary new cancer therapy to New Zealanders.

“When the Malaghan Institute first set out to run New Zealand’s inaugural CAR T-cell clinical trial, the facilities looked very different,” says Brigitta.

“There were no sleek machines, no automated systems and no shortcuts. It has taken literal blood, sweat and tears from Malaghan staff to make New Zealand’s first CAR T-cell trials a reality.”

Brigitta is the Malaghan’s resident GMP specialist.

“GMP stands for good manufacturing practice. It’s an international standard laid out by the World Health Organization which aims to make manufacturing medicines as safe as possible for humans,” explains Brigitta.

“It encompasses everything related to how you make a high-quality product intended for human consumption, from the cleanliness and airflow of the lab to how clearly and consistently you label different components to avoid mix-ups.”

Brigitta had already been involved in setting up GMP facilities for Malaghan’s previous clinical trial, testing a therapy for melanoma.

“We were just wrapping up the MELVAC trial when we got word that the Malaghan might be testing a new promising CAR T-cell therapy. I'd never heard of CAR T-cells before. I was asked to investigate the regulatory landscape of this therapy before we agreed to undertake the clinical trials for this new therapy.”

Brigitta and the team pored over all available documentation on this brand-new therapy. The more they read, the more excited they became.

CAR T-cell therapy works by taking the patient’s immune cells and modifying them genetically so they can recognise the cancer they are treating. These genetically modified cells are then multiplied so there are enough to infuse back into the patient to hunt down and destroy malignant cells.

Showing huge potential as the future of cancer therapy, the small team of dedicated scientists involved in evaluating the possibility of running a CAR T-cell trial saw that this could usher in a new era of treating blood cancers in NZ. However, they also knew that the challenge of building NZ's first CAR T-cell therapy trial from scratch would be Herculean.

There was no playbook and no existing infrastructure.

“If that wasn’t enough of a challenge, we were doing this on a shoestring budget with just 2.5 lab scientists,” says Brigitta.

The early days were relentless.

“We started by setting up a dedicated GMP production suite, suitable for manufacturing not just the CAR T-cells, but some of the required reagents as well. We did a lot of scrubbing in those early days. Every inch of the lab, including the air itself, had to be clean. We spent a lot of early mornings and late nights setting up the suite, cleaning, testing sterility, installing specialised equipment.”

Every procedure had to be written from scratch and the paperwork piled up fast. In Brigitta’s office, filing cabinets stretch from floor to ceiling, were packed full with the documentation she and the team produced to meet regulatory requirements.

Then came the testing. Before patient samples could be used, Malaghan staff were asked for blood donations.

“We could not use our own, because if we came into contact with any genetically modified cells specific to us, it could get risky. So we had to ask non-lab staff if they might volunteer. Everyone was eager to help, but our team did get the reputation of being vampires who needed a continuous supply of blood,” laughs Brigitta.

“CAR T-cells are unlike conventional one-size-fits-all drugs. These are living cells that are carefully tailored to the individual.”

Each patient’s cells had to be grown isolated from any other cells to avoid contamination, with complete cleaning of the lab between patient runs.

“We would modify and grow cells for each patient. Feeding them, encouraging them, at times, pleading with them to grow and be healthy,” Brigitta says.

“We knew what these cells represented, a last hope for patients who had exhausted all available treatments for their blood cancer.”

It was a very different kind of trial to the ones Brigitta had worked on before.

“Previously success took the form of complicated graphs showing specific immune cell activity, but for this trial it was black and white: patient survival. The result was tangible. Depending on the outcome, our team was either energised or deeply shaken. Either way, it made us work harder for these patients.”